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A traumatic spinal cord injury (SCI) induces a sequelae of events which conduce biochemical and cellular alterations. Here we compare the degree of spinal cord injury caused by the application of vascular clips, in mice lacking the 5-lipoxygenase and in the corresponding wild-type mice. Biochemical, immunohistochemical and functional studies revealed respectively an increase of neutrophils infiltration, of IL-1beta, TNF-alpha immunoreactivity, apoptosis (measured by Annexin-V staining) and loss of hind legs movement in SCI operated 5-LO wild-type mice. In contrast, the degree of (1) neutrophil infiltration at different time points, (2) cytokine expression (TNF-alpha and IL-1beta), (3) histological damage, (4) apoptosis, was markedly reduced in the tissues obtained from SCI operated 5-LO deficient mice and (5) the motor recovery was ameliorated.

Human immunodeficiency virus (HIV)-infection is characterized by loss of CD4+ T cells associated with high levels of immune activation, T-cell proliferation, and lymphocyte apoptosis. To investigate the role of intrinsic perturbations of cell-cycle control in the immunopathogenesis of acquired immunodeficiency syndrome (AIDS), we studied the expression of cell-cycle-dependent proteins in lymphocytes from HIV-infected patients. Cyclin B1 expression, Nucleolar Organizer Regions (NORs) number, and NORs area of distribution were all consistently increased in HIV-infected patients, but returned to normal after effective antiretroviral therapy, suggesting that viral replication is directly implicated in the genesis of the observed changes. Analysis of cyclin B1 intracellular turnover showed that the increased cyclin B1 expression is (1) caused by defective degradation in the presence of normal rates of synthesis, and (2) is temporally associated with decreased levels of ubiquitination. After in vitro activation of lymphocytes from healthy individuals, cyclin B1 and cdc25 expression and ubiquitination, p34 cdc2 activity, NORs morphology, and C23/nucleolin localization showed a 72- to 96-hour cyclic pattern that led to a biologic state similar to baseline. On the contrary, complex but consistent changes of the same indices followed activation of T lymphocytes from HIV-infected patients, resulting in a 5-fold increase in apoptosis. Overall, our data indicate that a profound dysregulation of cell-cycle control is present in lymphocytes from HIV-infected patients. This finding may provide a novel biologic link between immune activation, accelerated lymphocyte turnover, and increased apoptosis during HIV infection.